Identifying genes that maintain stable neural activity

描述(由申请人提供)：神经系统中兴奋和抑制的平衡似乎是许多神经退行性疾病的病因学中的一个关键因素。然而，人们对控制这种平衡的机制知之甚少。最近的研究表明，动态平衡机制监测和调节神经系统中细胞兴奋的水平。在果蝇的谷氨酸能突触上已经建立了一种神经元兴奋性的动态平衡调节模型，该模型与脊椎动物中枢和外周神经系统的突触动态平衡的模型类似。这项提议详细介绍了旨在阐明果蝇突触内稳态特性的实验。这种做法将是双重的。首先，将采用电生理学技术来表征突触内稳态的时程和可逆性。要做到这一点，将使用GAL4-UAS系统，该系统将允许有条件地破坏肌肉兴奋，从而有条件地激活内稳态信号。第二，将进行基因组规模的反向遗传学筛查，以确定与动态平衡信号有关的基因。为了进行这一筛选，我们提供了一个包含7260个果蝇dsRNA分子的文库。

DESCRIPTION (provided by applicant): The balance of excitation and inhibition in the nervous system appears to be a key factor in the etiology of many neurodegenerative diseases. However, the mechanisms that control this balance are poorly understood. Recent studies suggest that homeostatic mechanisms monitor and regulate the levels of cellular excitation in the nervous system. A model for the homeostatic regulation of neuronal excitability has been developed at a glutamatergic synapse in Drosophila that parallels models of synaptic homeostasis in the vertebrate central and peripheral nervous systems. This proposal details experiments designed to elucidate the properties of synaptic homeostasis in Drosophila. The approach will be twofold. First, electrophysiological techniques will be conducted to characterize the time-course and reversibility of synaptic homeostasis. To do this, the GAL4-UAS system will be used, which will allow conditional disruption of muscle excitation, and therefore, conditional activation of homeostatic signaling. Second, a genome-scale, reverse genetics screen to identify genes involved in homeostatic signaling will be performed. To conduct this screen, a library of 7260 Drosophila dsRNA molecules is available.